(1) The C-terminus of ClC-2 channel is directly phosphorylated by M phase-specific cyclin-dependent kinase, p34^<cdc2>/cyclin B, and de-phosphorylated by protein phosphatase 1, for which protein-protein interaction plays a crucial role. ClC-2 channel expressed in Xenopus oocytes is inhibited by phosphorylation and activated by dephosphorylation.(2) Western blot analysis and immunocytochemistry revealed that ClC-2 channel protein is expressed in dividing cells of the M phase of cell cycle, and promptly disappears after cell division. The PEST sequence is a signature of short-lived proteins via ubiquitination, and multiple PEST sequences are present in the C-terminus of ClC-2. Phosphorylation of ^<632>Ser of ClC-2 by p34^<cdc2>/cyclin B triggers ClC-2 channel ubiquitination, which underlines M phase-specific ubiquitination and degradation of ClC-2 channel protein.(3) ClC-3B is a chloride channel expressed predominantly in epithelial cells and is localized in its microvilli. ClC-3B interacts With EBP50, an epithelia-specific PDZ-containing protein, and thereby interacts with cystic fibrosis transmembrane conductance regulator (CFTR), a product of cystic fibrosis gene. ClC-3B chloride channel is activated by protein kinase A in the presence of CFTR, and is important in ionic transport across the epithelia.